Search

Microphysiological systems (MPS) are gaining broader application in the pharmaceutical industry but have primarily been leveraged in early discovery toxicology and pharmacology studies with small molecules. The adoption of MPS offers a promising avenue to reduce animal use, improve in-vitro-to-in-vivo translation of pharmacokinetics/pharmacodynamics and toxicity correlation, and provide mechanistic understanding of model species suitability. While MPS have demonstrated utility in these areas with small molecules and biologics, MPS models in cell therapy development have not been fully explored, let alone validated. Distinguishing features of MPS, including longterm viability and physiologically relevant expression of functional enzymes, receptors, and pharmacological targets make them attractive tools for nonclinical characterization. However, there is currently limited published evidence of MPS being utilized to study the disposition, metabolism, pharmacology, and toxicity profiles of cell therapies. This review provides an industry perspective on the nonclinical application of MPS on cell therapies, first with a focus on oncology applications followed by examples in regenerative medicine. [ABSTRACT FROM AUTHOR]

Primary hepatocyte sandwich cultures are useful for a variety of research applications where maintenance of metabolic competency is essential. To ensure an optimal hepatocellular phenotype, cells are seeded on collagen-coated dishes and embedded with an overlay of Matrigel. This culturing condition makes gene silencing by traditional reagent-mediated transfection methods challenging. Here, an siRNA delivery method in primary mouse hepatocytes that allows cells to be cultured with Matrigel overlay is described. This method delivers >80% mRNA silencing with minimal alterations in cell viability. A 96-well format allows for high-throughput RNA processing and downstream quantitative PCR applications and reduces time and resources. This format is particularly useful when experiments requiring many different sampling conditions (such as pharmacologic dose-response curves) are required., (© 2013 by John Wiley & Sons, Inc.)